I. AN INVESTIGATION OP THE VEHICLES AND THE MODES USED IN THE ADMINISTRATION OF PROGESTERONE: 1. Olive oil was found to be a suitable vehicle for the prolonged administration by injection (intramuscular or intraperitoneal) of steroid hormones in the rabbit, but ethyl cleate was unsuitable as it caused inflammation, irritation, and deposition of curd-like deposits at the site of repeated Intramuscular Injection. Non-uniform absorption of progesterone from ethyl cleate Injections was demonstrated. Ethyl cleate was suitable for single parenteral Injections. Neither ethyl oleate nor olive oil affected the morphology of the tissues studied after sacrifice of the animals. 2. Following single injections of progesterone, the excretion of urinary pregnanediol is significantly greater in the ovariectomized female than in the male rabbit, and following intraperitoneal than intramuscular injection. The significance of these results are discussed. II. AN INVESTIGATION OF THE ROLE OF THE UTERUS IN THE METABOLISM OF PROGESTERONE: 1. The "priming" phenomenon in the human described by Sommerville & Marrian (1950b) was not demonstrated In the rabbit, nor could it be confirmed in the human. The excretion of urinary pregnanediol of ovarlectomlzed and ovariectomized-hysterectomized female and normal male rabbits following prolonged progesterone administration did not differ significantly from each other. 2. Morphological changes induced by the exogenous progesterone could not be correlated with the urinary pregnanediol excretion. III. AN INVESTIGATION OF THE EFFECTS OF EXOGENOUS PROGESTERONE UPON THE MORPHOLOGY OF VARIOUS TISSUES IN THE RABBIT: 1. Administration of progesterone to the female rabbit caused degeneration of the ovarian follicles; and in the ovariectomized rabbit progesterone induced progestational proliferation of the uterus and vaginal mucification. 2. In the male rabbit, atrophy of the prostate. Cowper's glands, epididymis; hypertrophy of the uterus masculinus, seminal vesicles, vesicular gland; increased spermatogenesis and Increased secretory activity of the prostate, seminal vesicles, and vesicular gland, were all noted following progesterone administration. 3. In both sexes, varying doses of progesterone induced degeneration of the adrenal zona glomerulosa, fatty degeneration of the liver, glycogen depletion in the liver, cloudy swelling of the kidney tubules and enlargement of Bowman's capsule, and atrophy of the bladder epithelium. IV. A PRELIMINARY INVESTIGATION OF THE EFFECT OF OESTROGEN UPON THE CONVERSION OF PROGESTERONE TO URINARY PREGNANEDIOL: Oestrogens administered to rabbits (ovariectomized and ovariectomized-hysterectomized females) under various experimental conditions had no effect upon the excretion of urinary pregnanediol following progesterone administration. V. A PRELIMINARY INVESTIGATION OF THE ROLE OF THE LIVER IN PROGESTERONE METABOLISM IN THE RABBIT: 1. Excretion of urinary pregnanediol following single injections of progesterone in male rabbits was significantly increased by the induction of liver regeneration and decreased by severe liver and kidney damage. The significance of these observations with respect to present conceptions of the value of urinary pregnanediol studies both in the rabbit and in the human has been discussed. 2. The excretion of urinary glucuronic acid and sulphate (ethereal) in male rabbits was decreased by carbon tetrachloride administration. During progesterone administration to an ovarlectomlzed female rabbit, glucuronic acid excretion decreased and ethereal sulphate increased. 3. No unconjugated pregnanediol was found in the urine of carbon tetrachloride treated male rabbit following a single injection of progesterone. 4. No steroidal progesterone metabolites have been isolated from the rabbit faeces after intramuscular injection of progesterone. Attention is drawn to the significance of the role of both the liver and kidneys in progesterone metabolism, that is, in the reduction of progesterone to urinary pregnanediol. Many of the experiments are preliminary only (Section V), but indicate clearly the direction for further investigation.